Thesis (M.S.)--University of Missouri--Columbia, 1995. / Typescript. Includes bibliographical references (leaves 35-37). Also available on the Internet.

INTRODUCTION: Type 1 diabetes (T1D) is a lifelong disease that requires regular injection of insulin and blood glucose (BG) monitoring. Many diabetes technologies have been created to assist in the management of T1D, including insulin pumps and Continuous Glucose Monitoring (CGM). These systems have been shown to decrease treatment distress and improve glycemic control. However, the uptake of these systems is low due to both cost and other barriers such as discomfort of wear or psychosocial aspects. METHODS: A survey was administered to clinicians of people with diabetes to better understand their perception of patient related barriers to device use. This analysis compares two clusters of clinicians, named "Cautious" and "Ready" based on their readiness to promote CGM use in their patients. Both have positive attitudes towards technology, but the Cautious cluster perceives much higher barriers to device use in their patients than the Ready cluster. In this analysis, the individual barriers, prerequisites to CGM use, confidence in addressing barriers, and clinic staff resources are compared between clusters using independent means t-tests and Pearson chi-square analyses. RESULTS: Results indicate that the confidence in addressing the clinician-reported number 1 rated barrier to CGM use was significantly lower in the Cautious cluster. Also, most individual barriers were perceived significantly more heavily by clinicians in the Cautious cluster. No significant difference was found in prerequisites to CGM use or clinic staff resources between the clusters. DISCUSSION: Because no differences were found in clinician reported prerequisites to CGM use between clusters, it does not seem that the clinicians in the Cautious cluster expect more from their patients before using this technology. One possible explanation would be a clinical deficiency. However, since there was no difference in clinic staff resources, it is unlikely that the availability of these resources contributes to the increased perceived barriers. Thus, the problem may lie in the clinician themselves. One possible explanation for the increased perceived barriers by the Cautious cluster is their lack of confidence in addressing barriers. Our results show that the Cautious cluster is significantly less confident in addressing the #1 barrier their patients face to CGM use, which is most commonly listed as cost-related barriers such as cost of the device or insurance status. One possible solution to this lack of confidence in clinicians is increased education on ways to address and coach patients on cost-related barriers.

Class of 2009 Abstract / OBJECTIVES: An estimated 26.3 million Americans have Diabetes Mellitus (DM). Currently six classes of agents are approved for the treatments of Type 2 DM. Problems with current options have led to searches for new medications and adjunctive therapy. Prickly pear (Opuntia species) has been traditionally used by Mexicans and Pima Indians for the treatment of DM. This is a retrospective analysis of data obtained from a randomized placebo-controlled prospective experiment in 28 Type 2 DM rodents (ZDF). There were 2 negative control groups which consisted of non-DM rodents and ZDFs; each receiving water. The positive control group consisted of ZDFs who received rosiglitazone 4.75 mg/kg/day. The treatment group consisted of ZDFs who received 5-10 mL/kg/dose of Opuntia ficus indica (Jugo De Nopal) liquid, given twice daily. Weight, blood glucose and platelet aggregation were recorded and analyzed. At baseline, there were no significant differences in weight or blood glucose among ZDF groups. The lean control rodents had significantly lower blood glucose compared to the ZDF rodents (p<0.001). Treatment with Jugo de Nopal resulted in a statistically significant reduction in blood glucose (p<0.001), with a mean decrease in blood glucose of 7%. All treatment groups demonstrated a significant weight gain, however, the prickly pear group had significantly less weight gain than the rosiglitazone group (p=0.028). CONCLUSIONS: There was not a significant difference among the treatment groups with regard to platelet responsiveness. Further studies are necessary to determine the efficacy of prickly pear as a blood glucose lowering agent.

L2pB1 cells are a subset of B-1 B lymphocytes expressing programmed death ligand 2 (PD-L2) on their surface. They constitute 30-50% of B lymphocytes in the mouse peritoneal cavity and contribute to the production of natural IgM antibody. Previous studies have indicated a protective role of B-1 B cells in attenuating atherosclerosis and insulin resistance. We report that L2pB1 cells possess a unique IgM antibody specificity for phosphorylcholine (PC) and phosphatidylcholine (PtC) IgM enabling them to perform PC- and PtC-specific phagocytosis of PtC-nanoparticles. Here we demonstrate that induced depletion of L2pB1 in a transgenic mouse model with L2pB1-specific diphtheria toxin receptor (DTR) expression increases abdominal inflammation in the peritoneal cavity as well as the visceral adipose tissue in diet-induced obese (DIO) mice. L2pB1-depleted DIO mice also display increased triglycerides and blood glucose levels per gram of body weight relative to PBS-injected control DIO mice. Our results suggest that L2pB1 cells may play a role in anti-inflammatory regulation in DIO. Further investigation is required to discover how L2pB1 cells protect from obesity-induced inflammation and whether L2pB1 cells can provide cellular therapy to control chronic inflammation in obese patients. / 2018-06-16T00:00:00Z

Esse estudo teve como objetivo avaliar as alterações hemodinâmicas e do nível de glicemia decorrentes do uso do anestésico local articaína a 4% com epinefrina nas concentrações 1:100.000 (A100) e 1:200.000 (A200) em cirurgias periodontais na maxila, realizadas em diabéticos. Em relação aos anestésicos, foram avaliados: tempo de início de ação, duração da anestesia sobre os tecidos mole, analgesia pós-operatória, sangramento trans-operatório, qualidade da cicatrização, parâmetros hemodinâmicos e glicemia medidos durante as cirurgias. Para isso, 18 voluntários com idades entre 40 e 65 anos foram selecionados. Destes, 10 não apresentavam alterações sistêmicas (não diabéticos-não DM), enquanto 8 eram portadores de diabetes mellitus não insulinodependentes (DM), todos com condições periodontais semelhantes. Foram submetidos a cirurgias periodontais bilateralmente na região da maxila sob anestesia local com A100 e A200, de forma duplo-cega, randomizada e cruzada. O tempo cirúrgico foi semelhante para todos os grupos, e A100 e A200 mostraram-se igualmente eficazes para cirurgias periodontais. Foi utilizada quantidade idêntica de ambos anestésicos em todas as cirurgias (1 tubete; 1,8ml), o tempo cirúrgico foi semelhante em todos os procedimentos. O tempo de inicio de ação foi similar para todos, independentemente da concentração de epinefrina ou presença de diabetes. O tempo de duração da anestesia foi significativamente maior para os DM, sem haver correlação com a concentração de epinefrina. O sangramento trans-operatório foi significativamente maior nos pacientes diabéticos apenas na fase de incisão com A200. Nas demais fases, o sangramento foi muito semelhante entre DM e Não DM. A analgesia pós-operatória foi considerada excelente, refletindo na baixa ingestão de analgésicos (paracetamol), especialmente pelo grupo DM, independentemente da concentração de epinefrina. Quanto à cicatrização, não houve diferença entre os grupos. As mudanças transitórias nos parâmetros hemodinâmicos (frequência cardíaca-FC; pressão arterial-PA) tiveram pouco significado clínico, apesar de os diabéticos apresentarem certa tendência a elevação na PA nas fases de incisão e debridamento. Os diabéticos não apresentaram elevação da glicemia ao longo das fases cirúrgicas, independente da concentração de epinefrina presente na solução anestésica, ao passo que os não diabéticos mostraram que a maior concentração de epinefrina resulta num maior tempo para a normalização dos níveis glicêmicos. Concluindo, tais resultados mostram que A100 e A200 são equieficazes para a realização de cirurgias periodontais. Sendo assim, a utilização de anestésico com menor concentração de epinefrina (1:200.000) parece ser a melhor escolha para os indivíduos portadores de alterações sistêmicas como os diabéticos. / The present study compared the effect of articaine 4% associated with epinephrine in two different concentrations, 1:100.000(A100) and 1:200.000(A200), in periodontal surgeries performed in diabetic patients. We analyze hemodynamic parameters, blood glucose concentration, onset and duration of anesthetic action on soft tissues, intraoperative bleeding and wound healing. Eighteen volunteers, age range 40 to 65 years, with similar periodontal disease and conditions, were separate in two groups, type 2 diabetes mellitus (DM, 8 volunteers) or with no diabetes mellitus (Non DM, 10 volunteers). They´re submitted to a matched bilateral periodontal surgery in maxilla, under local anesthesia with either A100 or A200, in a double blind, randomized, crossed manner. The duration of surgery was the same for all groups, with A100 and A200 being equally effective for periodontal surgeries. Identical volumes of both anesthetic solutions were used (1 cartridge:1,8ml) in all surgeries. The anesthetic latency was similar in diabetics or non-diabetics for both epinephrine concentration. In diabetic patients the anesthetic duration was increased regardless the epinephrine concentration. Intraoperative bleeding only increased in diabetic patients with A200 during incision phase. The duration of postoperative analgesia was excellent, reflecting by a low intake of postoperative medications (paracetamol). Wound healing was relatively normal for all volunteers regardless the local anesthetic employed or presence of diabetes. The transient changes in blood pressure or hart hate were not clinically significant but the diabetic patients have some tendency to increase their blood pressure in some surgical phases. In diabetic subjects, blood glucose have no increase throughout surgical phases, regardless the epinephrine concentration present in the anesthetic solution, but the Non DM presents a prolonged time for normalize their blood glucose after A100. In conclusion, this study demonstrate that epinephrine concentration (1:100.000 or 1:200.000) in articaine 4% solution have the same efficacy for periodontal surgeries. Therefore, the formulation with a lower vasoconstrictor concentration (A200) seems to be the more adequate choice for patients with systemic diseases like diabetes.

Background: The postnatal failures of expression of the hepatic glucose-6-phosphatase system suggest there are developmental deficiencies in the mechanism to ‘switch-on’ this key enzyme of gluconeogenesis at the time of birth in both preterm and term infants. The evidence for hormonal regulation of this critical enzyme system in animal studies, in adult humans, and studies of cell lines make the possible failure of hormonal control around the time of birth an important hypothesis to test, but before this can be done, further studies of perinatal metabolism and its hormonal control need to be undertaken. Objective: To describe the hormonal and metabolic profiles of ‘unstressed’ term infants delivered by elective caesarean section. Methods: One hundred and fifty three women who had an elective caesarean section for a singleton pregnancy at term in Ninewells Hospital and Medical School, Dundee were recruited between July 2004 and April 2006. Maternal venous blood was taken for glucose and lactate estimations. Umbilical venous cord blood was obtained for the measurement of glucose, lactate, 3-hydroxybutyrate, free fatty acids, amino acids (alanine, arginine, citruline, cystine, GABA, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine ornithine, phenyalanine, serine,taurine, threonine, tyrosine and valine), insulin, glucagon, human growth hormone, cortisol, catechols (EPI, NE, DA, DOPA, DHPG, DOPAC) and their sulfated conjugates (EPI sulfate, NE sulfate, DA sulfate, DOPA sulfate, DHPG sulfate, DOPAC sulfate), and blood gas and acid-base profiles. Results The mean maternal glucose and lactate levels were 4.28 mmol/l and 1.8 mmol/l respectively. Three infants were hypoglycaemic with umbilical blood glucose levels of less than 2.6 mmol/l. The mean infant glucose and lactate levels were as expected for full term infants at 3.3 mmol/l and 2.2 mmol/l respectively. High mean levels of insulin and catechols were noted at birth. There was a significant positive association between umbilical venous cord glucose levels and maternal venous glucose levels (p=<0.001) but no association of umbilical venous cord glucose levels with amino acids, insulin, glucagon, human growth hormone, cortisol and catechols. Conclusions: This extensive data set of levels of metabolites and hormones in infants at birth acts as a reference source and will be valuable for evaluating any effects of antenatal or intrapartum factors on the hormonal and metabolic profiles of infants at birth as well as to investigate the mechanisms to ‘switch-on’ the key enzyme glucose-6-phosphatase. Objective: To describe the hormonal and metabolic profiles of ‘unstressed’ term infants delivered by elective caesarean section. Methods: One hundred and fifty three women who had an elective caesarean section for a singleton pregnancy at term in Ninewells Hospital and Medical School, Dundee were recruited between July 2004 and April 2006. Maternal venous blood was taken for glucose and lactate estimations. Umbilical venous cord blood was obtained for the measurement of glucose, lactate, 3-hydroxybutyrate, free fatty acids, amino acids (alanine, arginine, citruline, cystine, GABA, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine ornithine, phenyalanine, serine, taurine, threonine, tyrosine and valine), insulin, glucagon, human growth hormone, cortisol, catechols (EPI, NE, DA, DOPA, DHPG, DOPAC) and their sulfated conjugates (EPI sulfate, NE sulfate, DA sulfate, DOPA sulfate, DHPG sulfate, DOPAC sulfate), and blood gas and acid-base profiles. Results: The mean maternal glucose and lactate levels were 4.28 mmol/l and 1.8 mmol/l respectively. Three infants were hypoglycaemic with umbilical blood glucose levels of less than 2.6 mmol/l. The mean infant glucose and lactate levels were as expected for full term infants at 3.3 mmol/l and 2.2 mmol/l respectively. High mean levels of insulin and catechols were noted at birth. There was a significant positive association between umbilical venous cord glucose levels and maternal venous glucose levels (p=<0.001) but no association of umbilical venous cord glucose levels with amino acids, insulin, glucagon, human growth hormone, cortisol and catechols.

<p> </p><p>The aim of the study was auditing medical records examine postoperative blood glucose levels after undergoing CABG surgery. Furthermore the aim was to determine if the ward staff abides the local guidelines frame of reference concerning each ward, regarding blood glucose measurements and blood glucose levels. The study included 70 patients undergoing CABG surgery at the cardiothoracic surgery, Uppsala University Hospital. The study was conducted by retrospective medical record auditing. Studied factors were postoperative blood glucose levels, number of registered blood glucose measurements, a current diagnosis of DM and preoperative HbA_1c. Mean level of blood glucose levels stayed continuously above the local guidelines frame of reference for both TIVA/TIMA and the care ward throughout the continuity of patient care. The number of registered blood glucose measurements per postoperative day at TIVA/TIMA where within the local guidelines. The result showed that the local guidelines frame of reference concerning the ward were not reached. A difference could be seen between patients with DM and patients without DM regarding the previously mentioned factors. Preoperative elevated levels of HbA_1c could have influenced the number of postoperative blood glucose measurements. Recommendations will therefore be too audit the current local guideline that concerns the treatment, therapy goals and the number of blood glucose measurements. Establishing criterions regarding termination of blood glucose measurements and the transfer day between TIVA/TIMA and the care ward are recommended.</p><p> </p>

The aim of the study was auditing medical records examine postoperative blood glucose levels after undergoing CABG surgery. Furthermore the aim was to determine if the ward staff abides the local guidelines frame of reference concerning each ward, regarding blood glucose measurements and blood glucose levels. The study included 70 patients undergoing CABG surgery at the cardiothoracic surgery, Uppsala University Hospital. The study was conducted by retrospective medical record auditing. Studied factors were postoperative blood glucose levels, number of registered blood glucose measurements, a current diagnosis of DM and preoperative HbA1c. Mean level of blood glucose levels stayed continuously above the local guidelines frame of reference for both TIVA/TIMA and the care ward throughout the continuity of patient care. The number of registered blood glucose measurements per postoperative day at TIVA/TIMA where within the local guidelines. The result showed that the local guidelines frame of reference concerning the ward were not reached. A difference could be seen between patients with DM and patients without DM regarding the previously mentioned factors. Preoperative elevated levels of HbA1c could have influenced the number of postoperative blood glucose measurements. Recommendations will therefore be too audit the current local guideline that concerns the treatment, therapy goals and the number of blood glucose measurements. Establishing criterions regarding termination of blood glucose measurements and the transfer day between TIVA/TIMA and the care ward are recommended.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 109-113).

Hyperglycemia is prevalent in critical care, as patients experience stress-induced hyperglycemia, even with no history of diabetes. Hyperglycemia has a significant impact on patient mortality, outcome and health care cost. Tight regulation can significantly reduce these negative outcomes, but achieving it remains clinically elusive, particularly with regard to what constitutes tight control and what protocols are optimal in terms of results and clinical effort. Hyperglycemia in critical care is not largely benign, as once thought, and has a deleterious effect on outcome. Recent studies have shown that tight glucose regulation to average levels from 6.1–7.75 mmol/L can reduce mortality 17–45%, while also significantly reducing other negative clinical outcomes. However, clinical results are highly variable and there is little agreement on what levels of performance can be achieved and how to achieve them. A typical clinical solution is to use ad-hoc protocols based primarily on experience, where large amounts of insulin, up to 50 U/hr, are titrated against glucose measurements variably taken every 1–4 hours. When combined with the unpredictable and sudden metabolic changes that characterise this aspect of critical illness and/or clinical changes in nutritional support, this approach results in highly variable blood glucose levels. The overall result is sustained periods of hyper- or hypo- glycemia, characterised by oscillations between these states, which can adversely affect clinical outcomes and mortality. The situation is exacerbated by exogenous nutritional support regimes with high dextrose content. Model-based predictive control can deliver patient specific and adaptive control, ideal for such a highly dynamic problem. A simple, effective physiological model is presented in this thesis, focusing strongly on clinical control feasibility. This model has three compartments for glucose utilisation, interstitial insulin and its transport, and insulin kinetics in blood plasma. There are two patient specific parameters, the endogenous glucose removal and insulin sensitivity. A novel integral-based parameter identification enables fast and accurate real-time model adaptation to individual patients and patient condition. Three stages of control algorithm developments were trialed clinically in the Christchurch Hospital Department of Intensive Care Medicine. These control protocols are adaptive and patient specific. It is found that glycemic control utilising both insulin and nutrition interventions is most effective. The third stage of protocol development, SPRINT, achieved 61% of patient blood glucose measurements within the 4–6.1 mmol/L desirable glycemic control range in 165 patients. In addition, 89% were within the 4–7.75 mmol/L clinical acceptable range. These values are percentages of the total number of measurements, of which 47% are two-hourly, and the rest are hourly. These results showed unprecedented tight glycemic control in the critical care, but still struggle with patient variability and dynamics. Two stochastic models of insulin sensitivity for the critically ill population are derived and presented in this thesis. These models reveal the highly dynamic variation in insulin sensitivity under critical illness. The stochastic models can deliver probability intervals to support clinical control interventions. Hypoglycemia can thus be further avoided with the probability interval guided intervention assessments. This stochastic approach brings glycemic control to a more knowledge and intelligible level. In “virtual patient” simulation studies, 72% of glycemic levels were within the 4–6.1 mmol/L desirable glycemic control range. The incidence level of hypoglycemia was reduced to practically zero. These results suggest the clinical advances the stochastic model can bring. In addition, the stochastic models reflect the critical patients’ insulin sensitivity driven dynamics. Consequently, the models can create virtual patients to simulated clinical conditions. Thus, protocol developments can be optimised with guaranteed patient safety. Finally, the work presented in this thesis can act as a starting point for many other glycemic control problems in other environments. These areas include the cardiac critical care and neonatal critical care that share the most similarities to the environment studied in this thesis, to general diabetes where the population is growing exponentially world wide. Furthermore, the same pharmacodynamic modelling and control concept can be applied to other human pharmacodynamic control problems. In particular, stochastic modelling can bring added knowledge to these control systems. Eventually, this added knowledge can lead clinical developments from protocol simulations to better clinical decision making.